Project Grow Smart: A Randomized Controlled Trial to Assess Effects of Multiple Micronutrient Fortification on Frequency of Diarrhea and Acute Respiratory Infection among Infants in Rural South India

Abstract

Background: Infant anemia leads to poor neurophysiologic development and contributes to intergenerational cycles of poverty in India and low/mid-income countries causing high financial burden to society. WHO recommends implementing Multiple Micronutrient Powder (MNP) fortification strategies in areas with anemia prevalence > 20% among infants aged 6-23 months. Prior MNP studies designed to improve infant nutritional status without increased morbidity (thought due in part to bacterial utilization of unabsorbed iron) have been employed with mixed results. Objectives: The primary objective of this dissertation was to (obj1) assess effects of daily MNP fortification vs. control powder on infant diarrhea and Acute Respiratory Infection (ARI) over time. Secondary objectives included (obj2) comparing frequency of highly severe morbidity in MNP vs. control (diarrhea/ARI+treatment - tx) and (obj3) assessing whether MNP morbidity impact differs by intervention compliance (% of powder sachets consumed). Methods: Project Grow Smart was a randomized, controlled, double-blinded trial of infants in the rural Nalgonda district of Andhra Pradesh, South India. Participants (6-13 months) received either MNP or vitamin B2 control mixed with food daily for one year. Monthly morbidity questionnaires with 15-day recall were administered concurrently. Longitudinal binary-outcome regression was implemented to address study objectives using SAS 9.4. Results: 513 infants met inclusion criteria. Baseline demographic, growth, and biochemical measures were similar between MNP and control. Anemia at baseline was 68% overall. Follow-up was 78% and didn't differ between intervention groups. Comparing MNP vs. control, (obj1) no evidence of differences in diarrhea (OR=1.00, p=0.90) or ARI (OR=1.01, p=0.66) change over time was found. Similar MNP vs. control results emerged for diarrhea+tx (OR=0.99, p=0.78) and ARI+tx (OR=1.00, p=0.98) over time (obj2). Median compliance was 89.7% and did not differ between groups. Compliance > median did not modify MNP impact on diarrhea or ARI (obj3). Conclusions: Prior studies have shown harmful MNP impact on morbidity. Though Grow Smart's sample size was insufficient for evidence of intervention safety, MNP led to lower anemia prevalence vs. control with trend towards non-impact on morbidity. Lower MNP iron dose, higher socioeconomic status, and lower baseline morbidity prevalence in study population may explain result differences between studies.